Is UBTF p.Ser677Phe (c.2030C>T) pathogenic?

UBTF p.Ser677Phe (c.2030C>T) is classified Uncertain significance in UBTF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-15). AlphaMissense: ambiguous (0.3541); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with UBTF p.Ser677Phe (c.2030C>T)?

UBTF p.Ser677Phe (c.2030C>T) is associated with Inborn genetic diseases (ClinVar).

How common is UBTF p.Ser677Phe (c.2030C>T) in the general population?

UBTF p.Ser677Phe (c.2030C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about UBTF p.Ser677Phe (c.2030C>T)?

AlphaMissense predicts ambiguous (score 0.3541) — an in-silico prediction, not a clinical call.

UBTF p.Ser677Phe

c.2030C>T · VCV3813143

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3541 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Inborn genetic diseases

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.3541	ambiguous
REVEL	0.369	indeterminate
SaProt	LLR -10.27	damaging
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 633 bp · p 0.14 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,994 alleles

Overall 6.2e-05% 1/1,614,026 alleles · very rare exomes 1/1,461,848 · genomes 0/152,178 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: UBTF
Protein: p.Ser677Phe
Coding: c.2030C>T
MANE Select: NM_014233
Type: single nucleotide variant
Location: chr17:44207593 (GRCh38)

Full UBTF gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ubtf-p-ser677phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown